Glutamatergic synaptic transmission in the brain is mediated primarily by AMPA and NMDA receptor-channel subtypes. Both of these subtypes of receptor-channels also are subject to activity-dependent changes in synaptic strength, known as long- term potentiation (LTP) and long-term depression (LTD), which must reflect underlying changes in receptor-channel function. The precise neurobiological mechanisms responsible for phenomena such as LTP and LTD are as yet unknown, however, and many putative mechanisms involve properties of receptor-channels that are difficult or impossible to measure experimentally. We are collaborating with Dr. Michel Baudry (and also Dr. Gilbert Chauvet of the University of Angers, France; see Project ) to develop a detailed synaptic model of the glutamatergic synapse that includes molecular mechanisms of presynaptic release of neurotransmitter and postsynaptic mechanisms of the kinetics of both AMPA and NMDA receptors. Also included is the geometry of the synaptic cleft, and thus, the spatial relations between the presynaptic release sites and the postsynaptic receptors. This model is being used to help interpret experimental data generated in Dr. Baudry's lab (with funding from the NIMH) to resolve issues related to potential mechanisms underlying LTP and LTD.